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Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis
D-Aspartic acid is abundant in the developing brain. We have identified and cloned mammalian aspartate racemase (DR), which converts L-aspartate to D-aspartate and colocalizes with D-aspartate in the brain and neuroendocrine tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin...
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Published in: | Proceedings of the National Academy of Sciences - PNAS 2010-02, Vol.107 (7), p.3175-3179 |
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container_title | Proceedings of the National Academy of Sciences - PNAS |
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creator | Kim, Paul M Duan, Xin Huang, Alex S Liu, Cindy Y Ming, Guo-li Song, Hongjun Snyder, Solomon H |
description | D-Aspartic acid is abundant in the developing brain. We have identified and cloned mammalian aspartate racemase (DR), which converts L-aspartate to D-aspartate and colocalizes with D-aspartate in the brain and neuroendocrine tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin RNA in newborn neurons of the adult hippocampus elicits profound defects in the dendritic development and survival of newborn neurons and survival. Because D-aspartate is a potential endogenous ligand for NMDA receptors, the loss of which elicits a phenotype resembling DR depletion, D-aspartate may function as a modulator of adult neurogenesis. |
doi_str_mv | 10.1073/pnas.0914706107 |
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We have identified and cloned mammalian aspartate racemase (DR), which converts L-aspartate to D-aspartate and colocalizes with D-aspartate in the brain and neuroendocrine tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin RNA in newborn neurons of the adult hippocampus elicits profound defects in the dendritic development and survival of newborn neurons and survival. 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We have identified and cloned mammalian aspartate racemase (DR), which converts L-aspartate to D-aspartate and colocalizes with D-aspartate in the brain and neuroendocrine tissues. Depletion of DR by retrovirus-mediated expression of short-hairpin RNA in newborn neurons of the adult hippocampus elicits profound defects in the dendritic development and survival of newborn neurons and survival. Because D-aspartate is a potential endogenous ligand for NMDA receptors, the loss of which elicits a phenotype resembling DR depletion, D-aspartate may function as a modulator of adult neurogenesis.</description><subject>Adults</subject><subject>Amino Acid Isomerases - genetics</subject><subject>Amino Acid Isomerases - metabolism</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Blotting, Western</subject><subject>Brain</subject><subject>Cell lines</subject><subject>Cloning, Molecular</subject><subject>D-Aspartic Acid - biosynthesis</subject><subject>Dentate gyrus</subject><subject>Enzymes</subject><subject>Female</subject><subject>Gene expression</subject><subject>Genetic Vectors - genetics</subject><subject>Genotype & phenotype</subject><subject>Hippocampus</subject><subject>Hippocampus - metabolism</subject><subject>Immunohistochemistry</subject><subject>Inverted Repeat Sequences - genetics</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Molecular Structure</subject><subject>N methyl D aspartate receptors</subject><subject>Neurogenesis</subject><subject>Neurogenesis - physiology</subject><subject>Neurons</subject><subject>PC12 cells</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Retroviridae</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Stem Cells - metabolism</subject><subject>Tissues</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFkU1v1DAQhi0EokvhzAmIuPTStOP4K74gVaV8SJUQgp6tiTMJWWWTxU6Q-Pc4SrstXDhY9nieeTUzL2MvOZxxMOJ8P2A8A8ulAZ0-HrENT1GupYXHbANQmLyUhTxiz2LcAoBVJTxlRwVwIYzWG_b1Iu4xTDhRFtDTDiOdZi0NFHDqhjYbaA7jgH32Psc78jQL1M59esUM67mfVmqpil18zp402Ed6cXsfs5sPV98vP-XXXz5-vry4zr0q9ZQ3YK0xleVAKh1pag2yIlLeY-1FbbhHaz2h1uibuuC2qlArKUplEapKHLN3q-5-rnZUexqmgL3bh26H4bcbsXN_Z4buh2vHX64oJRSlSgIntwJh_DlTnNyui576Hgca5-iMVFbw1OD_ybRMDroQiXz7D7kd55D2F13auRQKzCJ3vkI-jDEGag5Nc3CLrW6x1d3bmipeP5z1wN_5-ABYKu_ljDNOcLMM-2oFtnEaw4GQoIQuxSLwZs03ODpsQxfdzbdFHngJShdK_AGrf7yH</recordid><startdate>20100216</startdate><enddate>20100216</enddate><creator>Kim, Paul M</creator><creator>Duan, Xin</creator><creator>Huang, Alex S</creator><creator>Liu, Cindy Y</creator><creator>Ming, Guo-li</creator><creator>Song, Hongjun</creator><creator>Snyder, Solomon H</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20100216</creationdate><title>Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis</title><author>Kim, Paul M ; 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subjects | Adults Amino Acid Isomerases - genetics Amino Acid Isomerases - metabolism Animals Biological Sciences Blotting, Western Brain Cell lines Cloning, Molecular D-Aspartic Acid - biosynthesis Dentate gyrus Enzymes Female Gene expression Genetic Vectors - genetics Genotype & phenotype Hippocampus Hippocampus - metabolism Immunohistochemistry Inverted Repeat Sequences - genetics Mice Mice, Inbred C57BL Molecular Structure N methyl D aspartate receptors Neurogenesis Neurogenesis - physiology Neurons PC12 cells Receptors, N-Methyl-D-Aspartate - metabolism Retroviridae Ribonucleic acid RNA Stem Cells - metabolism Tissues |
title | Aspartate racemase, generating neuronal D-aspartate, regulates adult neurogenesis |
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